Lyme disease is a multi-systemic infection and is caused by the pathogen Borrelia burgdorferi. The blacklegged tick, Ixodes scapularis, is the common vector for B. burgdorferi. The purpose of this project is to develop an anti-I. scapularis vaccine to block tick attachment and tick-mediated disease transmission. . Rabbits or guinea pigs infested with I. scapularis acquire antibody- mediated resistance to tick bites, a phenomenon known as "tick- immunity." We have developed a guinea pig model of host immunity against ticks. The tick-sensitized guinea pigs do not acquire Lyme disease when challenged with B. burgdorferi-infected I.. scapularis. Our plan is to determine which tick salivary gland antigens confer such host immunity, and subsequently produce them as recombinant antigens for evaluation as candidate vaccines. In preliminary experiments two recombinant proteins expressed from I. scapularis salivary gland cDNAs, Salp13 and Salp25D, induced tick-immunity. Phase I research will produce the recombinant proteins in prokaryotic and eukaryotic I expression systems. Guinea pigs and rabbits will be immunized with the purified antigens. We will then demonstrate host resistance to ticks, and inhibition of B. burgdorferi transmission from infected ticks. These experiments will lead to Phase II development of new vaccines to protect against multiple tick-borne pathogens. PROPOSED COMMERCIAL APPLICATIONS: A vaccine against Ixodes scapularis tick bites would potentially protect against several pathogens, including B. burgdorferi, the agent of human granulocytic ehrlichiosis, and Babesia microti. The commercial market would overlap with the market for LYMErix, a Lyme disease vaccine successfully sold by SmithKline Beecham.